People all over the world want to be healthy and look healthy. Having a good and balanced lifestyle comprising eating wholesome food, exercise, and minimizing external stresses like pollution, heat, dust, and ultra-violet (uv) radiation have been believed to give one a healthy body. In addition to the above lifestyle changes which also make a person look healthy, people use cosmetics to improve their external appearance. Two of the most important attributes to being healthy and looking healthy is a controlled body weight (not too overweight or too underweight) and external appearance of the exposed skin. While nutrition plays an important part in having a controlled body weight, external appearance is to an extent controlled by use of topically applied cosmetic products.
In tropical countries where people generally have dark skin, there is a desire to have lighter skin appearance. People who live far from the tropical areas e.g. the Caucasian people who generally have lighter skin, prefer to have an even tanned tone of their skin. Any exposure of their skin to sunlight, often leads to blotchy skin, referred to as freckles and in some cases they experience hyperpigmentation in localized areas of the skin.
To have lighter coloured or even toned skin colour, many cosmetic approaches are taken. One common approach is to include sunscreens or sunblocks in the cosmetic compositions. Sunscreens are generally organic compounds that work by absorbing ultra-violet radiation from the sun at a specified wavelength range thus not permitting the uv radiation from reaching the skin surface. UV radiation is believed to be the cause of skin coloration or tanning and if such tanning is uneven, it is disliked by the consumer. Sunblocks are generally inorganic compounds that act as physical barrier against a wide range of radiation from the sun (both uv and visible light).
Another approach is to include a skin lightening active in the cosmetic composition. Skin lightening actives are usually molecules or compositions which alter the formation of melanin in the skin through biochemical transformation in the skin thereby changing the colour and appearance of the skin. In human skin, formation of melanin pigment is initiated by the polymerization of the amino acid L-tyrosine, through a set of enzyme catalyzed as well as spontaneous chemical reactions. Amongst other things, this involves the action of the enzyme tyrosinase, present within the melanosomal compartment of melanocytes. Melanosomal contents are transferred from the melanocyte to multiple surrounding keratinocytes. The overall process is influenced by many hormones of which the melanocyte stimulating hormone (MSH), is a well studied one.
The present inventors have been working on developing novel skin lightening actives or new compositions for providing a skin lightening benefit. In the present invention, they have taken the approach to provide for novel peptides which preferentially bind to α-MSH (α-melanocyte stimulating hormone) so as to inhibit the binding of α-MSH on to the melanocortin 1 receptor (MC1 R). This inhibition provides benefits in the area of skin lightening. Use of peptides different from those disclosed herein for skin lightening which involve targeting the melanocyte have been disclosed earlier.
JP 2001 002527 (Lion) discloses a skin preparation for external use which includes 0.000001-30 weight percent based on total composition of a cell adhesion rearranging agent for melanocyte, e.g. peptides including Arginine-Glycine-Aspartic acid (RGD) sequence, peptides including an amino acid sequence of tyrosine-isoleucine-glycine-serine-arginine, pentoxyfeline, 3-deazaadenosine, derivatives of carboxamido, inositol polyamines, derivatives of salicylic acid and triterpenic acid, lactose, etc.
U.S. Pat. No. 5,126,327 (Lion) discloses a melanocyte-stimulating hormone inhibitor which has an amino acid sequence represented by formula [I], [II] or [III] as defined in the reference. It claims a melanocyte-stimulating hormone inhibitor and an external preparation to be applied to the skin which contains the inhibitor which prevent or cure the symptoms of chloasmata and freckles caused by an excess production of melanin by enhanced melanocyte function.
The present inventors have identified novel peptides which may be easily synthesized and may additionally provide synergistic benefits when used together. They found through extensive research involving a phage display technique that two specific peptides of seven amino acid sequence, specifically: Peptide (i) which has a specific low molecular weight (700 to 20 000) which has an amino acid residue of SEQ ID NO:1 -Leu-Ser-Arg-His-Val-Leu-Gln- (LSRHVLQ); or peptide (ii) having the amino acid residue of SEQ ID NO:2 -His-Gly-His-Pro-Phe-Ala-Pro- (HGHPFAP) preferentially bind to a-MSH (a- melanocyte stimulating hormone) so as to inhibit the binding of aMSH 0 n to M C 1 R. Further these peptides also have benefits in immunomodulation and modulation of body mass when they are used in topical or food compositions.
A search using basic local alignment search tool (BLAST) protein database search programs in the National Centre for Biotechnology Information (NCBI) database indicates that the exact same sequence of seven amino acids in peptide (i) has been reported as a part of a large protein or polynucleotide in natural occurring materials e.g in U.S. Pat. No. 7,344,860 (Bristol Myers Squibb Co.) and WO 2008 034648 (Metanomics). However the sequences reported therein have a molecular weight in excess of 27 000 Daltons and sometimes as high as 65 000 Daltons and do not provide the skin lightening and other benefits envisaged in the present invention. The inventors are not aware of the peptide (ii) being disclosed before.
It is thus an object of the present invention to provide for novel peptides which provide for skin lightening when incorporated in skin lightening products.
It is another object of the invention to provide for novel peptides which interact synergistically to provide for enhanced skin lightening as compared to the individual peptides when incorporated in skin lightening products.
It is yet another object of the present invention to provide for novel peptides which may be incorporated in topical or food products that provides for benefits like immunomodulation and/or modulation of body mass.